• 專任副教授
  • 李曉暉
  • Hsiao-Hui Lee
  • 02-2826-7000 ext. 7205/lab: ext. 6257 or 6213
  • 圖書資訊暨研究大樓9樓R923(office), R926(lab)
  • 專業領域
  • 分子生物學、細胞生物學、細胞生物力學
  • 研究方向
  • 當細胞貼附於細胞外基質時,與基質間的相互作用對於細胞的生長分化或行為動作的調控是非常重要的。我們實驗室結合分子生物學、細胞生物影像、生物工程的方法,探討透過調控細胞附著能力、細胞骨架動態與細胞內張力的訊息傳遞。我們逐步建立了RhoA/ROCK訊息在黏著點受c-Src與Shp2調控的分子機制,驗證了此機制在細胞因應基質軟硬度時調控細胞骨架與張力的生物重要性,並進一步發現alpha-actinin-4的參與。由於alpha-actinin-4分子對腎臟足細胞在腎絲球基底膜的附著與過濾能力扮演極關鍵角色,而腎臟足細胞的病變可說是腎絲球病變的關鍵原因,因此我們團隊目前的研究重點之一便是利用基因剔除細胞株以探討腎臟足細胞的細胞骨架調控機制,並將建立體外足細胞過濾分析系統,觀察過濾液壓對足細胞的力訊息傳遞與細胞骨架變化。

    (1) 探討腎臟足細胞與基質貼附的訊息傳遞與細胞骨架調控在腎絲球病變的相關性。
    (2) 建立過濾模式以分析過濾液壓對腎臟足細胞骨架與活性的影響。
    (3) 利用FRET影像系統觀測活細胞中Shp2等分子活性變化。
    (4) 以跨領域科學方法利用單分子模組了解細胞黏著點的張力需求

  • 教授科目
  • 生化及細胞分子生物學
  • 經歷
  • 2015 Feb.-present
  • 2013 Aug.-2015 Jan.
  • 2009 Aug.-2013 Jul.
  • 2011 Apr., Jul.-Sep., and 2012 Jan.-Feb.
  • 2006 Feb.-2009 Jul.
  • 學歷
  • 2006 Jan.


  • Chang CH, Lee HH*, Lee CH*. Substrate properties modulate cell membrane roughness by way of actin filaments. Sci Rep. 2017 Aug 22:7(1):9068 (*corresponding author)
  • Wu TH, Kuo YY, Lee HH, Kuo JC, Ou MH, Chang ZF*. Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization. Sci Rep. 2016 Jun 28;6:28685.
  • Tien SC, Lee HH, Yang YC, Lin MH, Chen YJ, Chang ZF*. Inhibition of HDAC6 reverses oncogenic Shp2-induced epithelial lumenogenesis defect independent of Cdc42. Nature Communications. 2016 Jan 19;7:10420. doi: 10.1038/ncomms10420.
  • Hsu CY, Chang ZF, and Lee HH*. Immunohistochemical evaluation of ROCK activation in invasive breast cancer. BMC Cancer. 2015 Dec 1;15(1):943. doi: 10.1186/s12885-015-1948-8. (*corresponding author)
  • Liu NY, Lee HH, Chang ZF, Tsay YG*. Examination of segmental average mass spectra from liquid chromatography-tandem mass spectrometric (LC-MS/MS) data enables screening of multiple types of protein modifications. Anal Chim Acta. 2015 Sep 10;892: 115-22. doi: 10.1016/j.aca.2015.07.032.
  • Wang HL, Yang CH, Lee HH, Kuo JC, Hur SS, Chien S, Lee KS, Hung SH, Chang ZF*. Dexamethasone-induced SGK1 increases Sec5/GEF-H1 interaction essential for adhesion-mediated tension. J Cell Sci. 2015 Oct 15;128(20):3757-68. doi: 10.1242/jcs.169961.
  • Tsai IJ, Chou CH, Yang YH, Lin WC, Lin YH, Chow LP, Lee HH, Kao PG, Liau WT, Jou TS*, Tsau YK*. Inhibition of Rho-associated kinase relieves C5a induced proteinuria in murine nephrotic syndrome. Cell Mol Life Sci. 2015 Aug;72(16):3157-71. doi: 10.1007/s00018-015-1888-0.
  • Kuo YC, Chang TH, Hsu WT, Zhou J, Lee HH, Ho HC, Chien S, and Lee KS*. Oscillatory shear stress mediates directional re-organization of actin cytoskeleton and alters differentiation propensity of mesenchymal stem cells. Stem Cells. 2015 Feb;33(2):429-42. doi: 10.1002/stem.1860.
  • Chuang HH, Liang SW, Chang ZF*, and Lee HH*. Ser1333 phosphorylation indicates ROCKI activation. J Biomed Sci. 2013 Oct 29;20:83. doi: 10.1186/1423-0127-20-83. (*corresponding author)
  • Lee HH*, Lee HC, Chou CC, Hur SS, Osterday K, del Álamo JC, Lasheras JC, and Chien S*. Shp2 plays a crucial role in cell structural orientation and force polarity in response to matrix rigidity. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2840-5. doi: 10.1073/pnas.1222164110. (* corresponding author)
  • Pan YR, Cho KH, Lee HH, Chang ZF, and Chen HC. Protein tyrosine phosphatase SHP2 suppresses podosome rosette formation in Src-transformed fibroblasts. J Cell Sci. 2013 Jan 15;126(Pt 2):657-66. doi: 10.1242/jcs.116624.
  • Chuang HH , Yang CH, Tsay YG, Hsu CY, Tseng LM, Chang ZF*, Lee HH*. ROCKII serine 1366 phosphorylation reflects the activation status. Biochem J. 2012 Apr 1;443(1):145-51. doi: 10.1042/BJ20111839. (*corresponding authors)
  • Lee HH, Tien SC, Jou TS, Chang YC, Jhong JG, and Chang ZF. c-Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics. J Cell Sci. 2010 Oct 1;123(Pt 19):3368-77. doi: 10.1242/jcs.071555.
  • Lee HH and Chang ZF. Regulation of RhoA-dependent ROCKII activation by Shp2. J Cell Biol. 2008 Jun 16;181(6):999-1012. doi: 10.1083/jcb.200710187. (Faculty of 1000 in Biology, Recommended)
  • Chang YC, Lee HH, Chen YJ, Bokoch G and Chang, ZF. Contribution of guanine exchange factor H1 in phorbol ester-induced apoptosis. Cell Death Differ. 2006 Dec;13(12):2023-32.
  • Chang ZF and Lee HH. RhoA signaling in phorbol ester-induced apoptosis. J Biomed Sci. 2006 Mar;13(2):173-80. (Review)
  • Lee HH, Chien CL, Liao HK, Chen YJ, and Chang ZF. Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic cells: a novel nuclear export dependent on Rho-associated kinase activation. J Cell Sci. 2004 Nov 1;117(Pt 23):5579-89.
  • Lai LP, Lin JL, Lin CS, Yeh HM, Tsay YG, Lee CF, Lee HH, Chang ZF, Hwang JJ, Su MJ, Tseng YZ, Huang SK. Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation. J Cardiovasc. Electrophysiol. 2004 Feb;15(2):214-23.
  • Lin CM, Chen CT, Lee HH, Lin JK. Prevention of cellular ROS damage by isovitexin and related flavonoids. Planta Med. 2002 Apr;68(4):365-7.


  • 專利名稱:Reagents for probing ROCKs activation.
    發明人:Zee-Fen CHANG, Hsiao-Hui Lee
    公告號 (TW):I460274 (Taiwan patent approved at 2014)
    公開號 (US):US9017952 B2 (US patent approved at 2015)